This 4 year study aims to evaluate Naltrexone (N), Lofexidine (L) and their combination (N+L) in conjunction with psychosocial treatment to prevent relapse in detoxified heroin addicts. We hypothesize that each of these medications will be helpful, but that the combination of N+L will be more effective than either medication alone. The study will be done in collaboration with researchers at the Pavlov University in St. Petersburg, Russia. Subjects will be 280 male and female heroin addicts who have been detoxified in one of two addiction treatment hospitals in St. Petersburg. Patients must have a family member willing and able to supervise medication compliance. After giving informed consent and passing a narcan challenge, subjects will be randomly assigned to one of four groups of 70 patients each: N 50 mg a day + L placebo; L 2.4 mg a day + N placebo; N+L ; or N placebo + L placebo. All patients will receive biweekly clinical management/compliance enhancement counseling and treatment will last 6 months. Assessments will be at baseline, at each biweekly appointment, and at 3 and 6-months following the end of treatment. Primary outcomes will be drop-out and relapse to heroin dependence, adherence to medication, and protracted withdrawal symptoms; secondary outcomes will be HIV risk, psychiatric symptoms, and other measures of adjustment. This study will extend previous work at Pavlov Medical University with naltrexone and at Yale University with Iofexidine, will provide information about the efficacy of these medications in preventing relapse in a cultural setting where agonist substitution therapy is not available, and also provide data on the long term course of heroin addiction in this cultural setting.